Biology subjects

Tian, Y.

Publications and source records attributed to Tian, Y..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

Mast cell extracellular granules are bioactive condensates driven by heparin and polyamine

Biomolecular condensates are membraneless bodies that organize biochemical reactions typically within cells. However, the roles of condensates in extracellular space--where conditions differ substantially from intracellular space--remain poorly understood. Here, we report mast cell extracellular granules (MCEGs), a stable membraneless entity, are condensates assembled via electrostatic interactions between glycosaminoglycans and polyamines. Disrupting polyamine synthesis or trafficking blocks MCEG formation and compromises the storage of proteases and cytokines. Granules reconstituted with heparin and spermine are sufficient to enrich mediators such as CPA3 and TNF, maintaining an elevated pH and higher concentrations of calcium and zinc compared to the extracellular milieu. This unique environment enhances CPA3 enzymatic activity. Furthermore, the granules increase TNF binding and its bioactivity toward endothelial cells. Together, we reveal MCEGs as functionally active biomolecular condensates with distinct biochemical and immunological properties; MCEGs are formed through sugar-metabolite interactions, expanding the mechanisms of condensate assembly beyond classical protein-protein and protein-RNA interactions.

cell biology↗

bioRxiv2025

Spatial proteomic mapping of the human and mouse retina using IBEX

PurposeTo generate a comparative spatial proteomic atlas of the human and mouse retina using a refined highly multiplexed immunohistochemistry technique called Iterative Bleaching Extends Multiplexity (IBEX). MethodsWe refined the IBEX workflow by integrating an antibody removal option alongside chemical bleaching. This dual strategy enabled removal of the entire antibody complex allowing for the flexible use of antibodies from the same host species across iterative cycles. Spatial proteomic data were cross-correlated to existing scRNAseq datasets. We also coupled this workflow with super-resolution imaging via deconvolution and applied it to the retina of healthy human, mouse and the Crb1rd8 mouse model. ResultsWe successfully imaged over 25 protein markers on human and mouse tissue sections, to generate spatial atlases of the major retinal cell populations. Cross-species protein expression was compared to scRNAseq datasets to identify protein and transcript disparities. Super-resolution IBEX delineated the ultrastructural features of the outer limiting membrane (OLM), identifying CD44 as a core structural component tightly co-localised with a highly organised F-actin belt within Muller glial endfeet. Using the Crb1rd8 mouse model, disruption of this complex was spatially associated with rosette formation and OLM structural failure. ConclusionSpatial proteomic atlases of the human and mouse retina were generated and correlated to transcriptional data, revealing insights into the arrangement of major retinal cell populations and OLM structure.

neuroscience↗

bioRxiv2025

Recapitulating Patient-to-Patient Colorectal Cancer Tumor Heterogeneity Using Patient-Derived Xenograft Cells in an Engineered Tissue Model

Establishing in vitro cancer models that more closely recapitulate patient tumor microenvironmental heterogeneity, including variations in stromal cells and mechanical properties that influence colorectal cancer (CRC) progression, is crucial for advancing CRC research. This study evaluated the ability of 3D engineered CRC-PDX (3D-eCRC-PDX) tissues to recapitulate the heterogeneity found between patient-derived xenograft (PDX) tumors from three CRC patients (stage II, III-B, and IV). To form the 3D-eCRC-PDX tissues, CRC-PDX tumor cells were encapsulated in PEG-fibrinogen hydrogels and maintained for 29 days in vitro. 3D-eCRC-PDX tissues recapitulated key patient-specific tumor characteristics. During long-term culture, 3D-eCRC-PDX tissues mimicked the patient-specific growth rates of the originating CRC-PDX tumors. Importantly, tumor cellular subpopulations, including the ratio of human cancer cells to mouse stromal cells and the ratios of proliferative human cancer cells and CK20+ cells were maintained in 3D-eCRC-PDX tissues, unlike in 2D cell culture. Differences in mechanical stiffness between the originating CRC-PDX tumors were also recapitulated by the 3D-eCRC-PDX tissues. Principal component analysis of transcriptomic data clustered 3D-eCRC-PDX tissues and CRC-PDX tumors together by patient, indicating similar gene expression profiles. These findings highlight the potential of 3D-eCRC-PDX tissues as a promising tool for CRC research, capable of maintaining patient-specific tumor microenvironment heterogeneity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/693817v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@16c19baorg.highwire.dtl.DTLVardef@d3a75org.highwire.dtl.DTLVardef@79026forg.highwire.dtl.DTLVardef@8ede45_HPS_FORMAT_FIGEXP M_FIG C_FIG Statement of SignificanceThis study establishes engineered colorectal cancer tissues formed using PEG-fibrinogen and patient-derived xenograft (PDX) tumor cells for modeling inter-patient tumor heterogeneity. In vitro models that preserve patient tumors biological and structural heterogeneity are central to the development of more predictive and reproducible preclinical cancer models. Here engineered tissues replicated patient-specific tumor growth dynamics, sustained key cancer and stromal cell subpopulations, recapitulated originating PDX tumor stiffness, and sustained patient-specific patterns of gene expression. This work demonstrates the long-term culture of cells from patient xenografts in engineered colorectal cancer tissues, enabling sustained preservation of critical patient tumor-specific microenvironmental characteristics in vitro.

bioengineering↗

bioRxiv2025

The shifting dynamics of ancestry and culture at a post-Roman crossroads

The collapse of the western Roman Empire in the 5th century created a period of geopolitical upheaval, driven by Barbarians dispersing into the former Empire and reshaping post-Roman communities. While there is now evidence for a major genetic impact of these migrations into specific regions of Europe, it is unknown whether these changes in ancestry were uniform across the continent. We investigate present-day Slovenia, a crucial crossroad connecting the Roman East and West and the gate to Italy during the Langobard invasion. We conducted paleogenomic and isotopic analyses of 410 individuals from 21 sites across Slovenia and Cividale (Italy), establishing a longitudinal transect, spanning eight centuries. During Late Antiquity, despite changes in burial artifacts, kinship practices, and settlement structures reflecting a shift in culture, we find high levels of genetic continuity with the local Late Roman population and reduced mobility. However, demographic turnover began during the 8th century, when communities with northeastern European ancestry and distinct cultural practices entered the region, gradually advancing westward over the span of three centuries, replacing the local populations. This shows that cultural change in post-Roman Europe could be decoupled from genetic change in transit zones, demonstrating a dynamic spatiotemporal process across the continent.

genetics↗

bioRxiv2025

Genome-wide CRISPR screen reveals PEX11B as a host restriction factor against ORFV through membrane fluidity regulation

Host-pathogen interactions are shaped by cellular restriction factors that direct antiviral defenses. We built the first ovine genome-wide CRISPR knockout library in sheep testis (OA3.Ts) cells, targeting all protein-coding genes. Using this platform, we identified PEX11B, a peroxisomal membrane regulatory protein, as a strong restriction factor against orf virus (ORFV) infection. Removing PEX11B increased viral susceptibility and triggered severe cytopathic effects with membrane fusion and syncytia formation. Mechanistic studies showed that PEX11B knockout harmed peroxisomal integrity and disrupted lipid metabolism. This led to greater plasma membrane fluidity, creating a proviral environment that allowed more viral entry and replication. These results reveal a new antiviral function for PEX11B in blocking viral infection and underscore the importance of peroxisomal regulation in host-virus interactions.

microbiology↗

bioRxiv2025

Neural ensembles for music production recruit more language instruments as rhythmic complexity increases

Language and music, two core forms of human communication, both rely on rhythmic control. To date, the neural ensembles supporting their real-time production are not fully characterized. Using rapid phase-encoded fMRI, we mapped the spatiotemporal brain dynamics of overt language and music production under varying rhythm control demands. We observed overlapping hemodynamic traveling waves across domains, with auditory-motor regions activated earlier, followed by visual, posterior parietal, and Sylvian parietal-temporal (Spt) regions, supporting sensorimotor transformation and online monitoring of production. Increasing rhythmic complexity elicited slower and stronger activations in both domains: compared with baseline, regular rhythm control elicited delayed and amplified responses, while irregular rhythm control produced the slowest and strongest responses. During music production, rhythm-related activity expanded into frontal and temporal language regions, suggesting that higher rhythmic demands engage language resources. These findings reveal dynamic neural ensembles that can flexibly reconfigure shared resources to support temporal precision in sequence production.

neuroscience↗

bioRxiv2025

Gut Microbiota-derived Adenosine Determines the Efficacy of Electroconvulsive Therapy for Depression

Electroconvulsive therapy (ECT) is a final procedure for major depressive disorders (MDD). However, the effectiveness of ECT in treating MDD patients varies. Here we identified gut microbiota as a potential restraining factor of ECT efficacy. By using a 5-day electroconvulsive shock (ECS) in depression mouse model of chronic restraint stress (CRS), it was observed that the antidepressant effect of ECS was suppressed after antibiotics (ABX)-induced microbiota dysbiosis, which also resulted in elevated c-Fos expression of CRH neurons in paraventricular nucleus of hypothalamus (PVN) and increased serum corticosterone levels after ECS. Metabolomic analysis revealed the critical involvement of microbiota associated purine metabolism, and the supplement of gut microbiota-derived adenosine was able to recover the antidepressant effect of ECS in ABX-treated CRS mouse model. Based on the neural tracing from colon to brain and the immunofluorescence staining, it was surmised a gut-brain axis originated from Adora1-expressing cells in colon mediate this biological process. Furthermore, adenosine supplement alleviated the further deterioration of post-ECS memory loss and impairment of synaptic plasticity induced by ABX-treatment as well. Our findings suggest a potential role of microbial adenosine metabolism in ECT efficacy determination and side effect protection, highlights potential application of adenosine supplement in antidepressant therapies of those depression patients with microbiota dysbiosis.

systems biology↗

bioRxiv2025

A Study on the Pharmacokinetic/Pharmacodynamic Profiles of the Novel PPAR Pan Agonist Chiglitazar Sodium in Rats with Hypoalbuminemia

ObjectiveTo compare the changes in the pharmacokinetic/pharmacodynamic (PK/PD) profiles of Chiglitazar Sodium between healthy rats and those with hypoalbuminemia, and to evaluate the medication safety of Chiglitazar in rats with hypoalbuminemia. MethodsLiquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method was employed to determine the plasma concentration ofChiglitazar Sodium in both healthy rats and rats with hypoalbuminemia after administration. Pharmacokinetics were calculated based on the measured data. Blood glucose levels were monitored and recorded in both groups to observe pharmacodynamic changes. ResultsPharmacokinetic analysis revealed that, compared to the healthy group, only the Tmax in the hypoalbuminemia group was significantly earlier by 34.3% (P<0.001), while other pharmacokinetic parameters showed no significant differences. Pharmacodynamic studies indicated that blood glucose levels remained stable in both healthy rats and rats with hypoalbuminemia during the 0.25-10 hour monitoring period. ConclusionExcept for Tmax, there were no significant differences in PK/PD parameters between rats with hypoalbuminemia and healthy rats. Blood glucose levels remained stable in both groups after oral administration of Chiglitazar Sodium. The animal experimental results suggest that, under normal conditions, hypoalbuminemia does not affect the pharmacokinetic and pharmacodynamic profiles of Chiglitazar Sodium.

pharmacology and toxicology↗

bioRxiv2025

Structural basis for lipid binding by the blood protein vitronectin, a component of HDL

Vitronectin (Vn) is a multifunctional blood glycoprotein involved in cell adhesion and migration, blood coagulation, and inflammation. It is a component of the high-density lipoprotein (HDL) proteome, and often found associated with the calcified, lipid-rich, protein deposits that are a hallmark of age-related macular degeneration, Alzheimers disease, atherosclerosis and other aging-related diseases. Here we explored the molecular basis for lipid binding by Vn using isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) and all-atom molecular dynamics (MD) simulations. The data reveal a hydrophobic groove on the surface of the hemopexin-like (HX) domain of Vn, that is capable of binding phosphatidylcholine (PC). Conformational landscape analyses of multiple, independent MD simulations identify key structural motifs and intermolecular contacts mediating the association of Vn with PC, and show that lipid binding is guided by interactions with positively charged and hydrophobic residues that organize the lipids in a tail-to-tail bilayer-like arrangement within the groove. Collectively, the data establish a comprehensive structural model for Vn association with HDL and provide mechanistic insight into its accumulation within lipid-rich deposits characteristic of age-related pathologies.

biophysics↗

bioRxiv2025

Complete and haplotype-resolved maps of genomic and epigenetic discordance in monozygotic twins

Telomere-to-telomere (T2T) genome assemblies are indispensable for accurate detection of genetic variation and for resolving complex repetitive regions. Monozygotic (MZ) twin pedigrees provide a powerful model to investigate de novo mutations (DNMs), however, comprehensive, haplotype-resolved analyses of structural variation (SV), allele-specific inheritance in complex regions, and DNA methylation in diploid human genomes remain limited. Here, we generated complete, haplotype-resolved T2T assemblies for two female twins (C33 and C35) from a Han Chinese pedigree by integrating complementary, state-of-the-art sequencing technologies. The resulting T2T-C33 and T2T-C35 assemblies are highly contiguous and complete, with Genome Continuity Inspector (GCI) scores of 74.94 (maternal) and 77.94 (paternal), and consensus quality values (QV) >75 (k = 21). We comprehensively cataloged 62 inter-twin single-nucleotide variants (SNVs), 15 small indels, and identified both shared and private DNMs, revealing nascent genomic divergence between the MZ twins. Focused interrogation of complex regions uncovered pronounced haplotype-specific length polymorphisms and structural heterogeneity within centromeric higher-order repeat (HOR) arrays. Notably, we observed extensive HOR copy-number variation between haplotypes, including a large copy-number difference on maternal chromosome 18, underscoring dynamic HOR array evolution even among genetically identical individuals. Concurrently, genome-wide DNA methylation profiling delineated allele-specific epigenetic variation that may contribute to phenotypic discordance. Together, these high-quality, diploid T2T genomes from a Han Chinese pedigree provide a valuable resource for population-aware genomics and reveal fine-scale, haplotype-specific divergence in MZ twins. Our results advance understanding of repeat dynamics, centromeric architecture, epigenetic variation and the spectrum of human genomic variation at single-base and structural scales.

genomics↗

bioRxiv2025

Sulcal landmarks reveal lineage-specific trajectories and multi-scale specialization of the mammalian cortex

An important topic of evolutionary neuroscience is to understand how brain function and structure across evolutionary time. In the absence of functional data for ancestral species, studies often rely on structural features such as cortical volume or surface area. However, atlas-based metrics derived from human or a few model organisms lack biological interpretability across species with divergent cortical architectures. Here, we investigate sulcal pits--the locally deepest points of cortical folds--as conserved, atlas-independent landmarks that provide a robust basis for cross-species comparison. Using cortical surface reconstructions from 90 mammalian species, we show that sulcal pit distribution patterns partly recapitulate phylogenetic relationships, independent of overall brain size (volume and surface area), and vary systematically with ecology and lifestyle. By tracing pit-based evolutionary trajectories from 80 million years ago to the present, we found pronounced differences across ecological and behavioral categories, indicating that cortical folding has diversified in close association with species habitats, lifestyles, and social structures. Using sulcal pits, we identified Homo sapiens-specific regions and species-shared regions. The Homo-specific areas were functionally associated with higher cognitive and emotional processes, distinguished by unique histological features, enriched for gene sets related to neural regulation, and exhibited markedly different cell-type abundance profiles compared to shared regions. Together, these results establish sulcal pits as a robust, evolutionarily informative feature for cross-species cortical alignment, offering new insights into the structural innovations underlying brain evolution study.

evolutionary biology↗

bioRxiv2025

Frequency-dependent Inhibition during Deep Brain Stimulation of Thalamic Ventral Intermediate Nuclei

Deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (Vim) has been a standard therapy for essential tremor. It has been shown that high frequency ([≥]100Hz) DBS suppresses Vim neuronal firing and tremor activity, however, the underlying mechanisms are not fully understood. Here, we use in vivo recordings (single-unit) of Vim neurons (n=19, people with essential tremor) during different DBS frequencies to investigate whether neuronal suppression during high-frequency DBS occurs at synaptic/cellular levels (e.g., cell inhibition due to synaptic depression/fatigue during high-frequency DBS) or is influenced by network-level effects (e.g., recurrent inhibition). We propose a theoretical framework that explains DBS effects at both cellular and network levels, i.e., (continuous) high-frequency DBS not only depresses synapses projecting to Vim but also enables the recruitment of inhibitory neurons. A transient burst in the spiking activity of Vim during high-frequency DBS, prior to neuronal suppression, is likely providing sufficient network engagement to recruit inhibitory neurons that are silent during low-frequency DBS. Further, we detected a positive-going evoked-field potential effect, hereafter referred to as quasi-evoked inhibition, during high-frequency (100 Hz and 200 Hz) Vim-DBS in four out of 19 recording sites. Interestingly, it was observed that (i) neuronal suppression is stronger in these four neurons (P < 0.05), implying that inhibitory engagement during high-frequency DBS can further suppress neuronal firing, and (ii) quasi-evoked inhibition emerges after the transient burst (P < 1.00 x 10-7), i.e., the latter may give rise to the former. By removing DBS artifacts with a novel algorithm and characterizing the dynamics of quasi-evoked inhibitory activity, we showed that the likelihood of occurrence of this inhibitory activity negatively correlated with the instantaneous firing rate (P < 1.00 x 10-5). These results suggest that an excitatory-inhibitory balance is likely regulating Vim activities during high-frequency DBS. Our findings shed light on potential network mechanisms underlying Vim-DBS, which can provide insight for optimizing DBS by designing new stimulation patterns.

neuroscience↗

bioRxiv2025

Brain Preparedness for Active Forgetting: Cortisol Awakening Response Proacts Prefrontal Control Over Hippocampal-Striatal Circuitry

Stress-related psychiatric pathologies (e.g., rumination in depression, intrusive memories in PTSD) involve impaired inhibitory control over emotional memories and disrupted cortisol circadian rhythms. However, how these mechanisms interact to support adaptive forgetting remains unclear. Here, by integrating multi-modal neuroendocrine profiling with fMRI-based memory suppression in 90 participants, we demonstrate that the cortisol awakening response (CAR)--a circadian surge priming the brain for daily demands--proactively and selectively enhances suppression of recently acquired but not overnight-consolidated emotional memories. This time-dependent facilitation manifests through dual neural mechanisms: Robust CAR broadly amplifies dorsolateral prefrontal cortex (dlPFC) engagement during suppression attempts and specifically strengthens top-down dlPFC control over hippocampal-striatal circuits exclusively for recent traces. Our findings bridge circadian biology, systems neuroscience, and clinical psychopathology to establish CAR as a neuroendocrine preparedness mechanism that proactively configures adaptive forgetting circuits across sleep-wake cycles, thereby informing circadian-based interventions for stress disorders.

neuroscience↗

bioRxiv2025

Effects of arginine on the interfacial behavior of proteins

HypothesisProtein adsorption at fluid-fluid interfaces can induce conformational rearrangements and promote aggregation. Arginine, as an amino acid is known to attenuate protein-protein interactions and lower the viscosity of protein formulations. Given its surface-active properties, we hypothesize that arginine may be effective in limiting aggregation at fluid-fluid interfaces. ExperimentsInterfacial rheology of Etanercept (Enbrel), Immunoglobulin G1 (IgG1), and Bovine Serum Albumin (BSA) was characterized across a range of concentrations, with and without L-arginine Hydrochloride. The interfacial response was examined in both linear and nonlinear regimes.{zeta} -potential was also measured for selected formulations to evaluate the relationship between electrostatic characteristics and the rheological outcomes. FindingsBased on both linear and nonlinear interfacial rheology results, arginine generally weakened protein-protein interactions; however, the effect depends on protein identity and concentration. In arginine-containing formulations, Enbrel and BSA displayed only minor variation in interfacial viscoelasticity between 0.01 and 1 mg/mL, particularly during prolonged aging; in contrast, IgG1 showed larger concentration-dependent differences. These results strengthen predictive frameworks for interfacial stability and guide the rational design of protein-amino acid biopharmaceutical formulations. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/674647v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@10a0bc8org.highwire.dtl.DTLVardef@8b9be7org.highwire.dtl.DTLVardef@1a88e43org.highwire.dtl.DTLVardef@113d5a9_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2025

Cross-species brain circuitry from diffusion MRI tractography and mouse viral tracing

Understanding how brain networks support cognition requires knowing not only which regions are connected but the direction in which neuronal signals propagate. However, directed connectivity cannot be measured non-invasively in primates or humans, limiting systems-level inference. Here we integrate projection polarity from [~]1,200 mouse viral tracing experiments with species-specific diffusion MRI tractography to construct directed connectomes across mouse, marmoset, macaque, and human. Using a common cross-species atlas, we developed a path efficiency metric that balances projection strength against axonal length and applied shortest-path algorithms to quantify directional influence. This framework revealed conserved and divergent organization: the entorhinal-hippocampal projection was the most efficient in all species; humans showed strengthened anterior insula-superior temporal pathways; macaques exhibited peak inferior temporal outflows; and marmosets maintained disproportionately strong olfactory influence. These results provide a scalable and ethically feasible approach for modeling directed neuronal signaling across species.

neuroscience↗

bioRxiv2025

A common cross-species atlas of cortical gray matter

Translational neuroscience requires consistent anatomical frameworks to compare brain organization across species despite differences in size and specialization. Existing atlases are species-specific, limiting cross-species analyses. Here we developed a hierarchical common atlas delineating homologous cortical and subcortical gray matter regions across mouse, rat, marmoset, rhesus macaque, and human, built upon population-averaged minimal deformation templates and uniform tissue segmentation. The atlas was validated through cross-atlas Dice similarity against established human parcellations, cross-scale containment against species-specific atlases, cross-species geometric consistency of regional positioning, and comparison of independent mouse and marmoset invasive tracer connectivity, with a per-region homology confidence index quantifying the strength of each regional assignment. Cross-species tracer comparison revealed a structured gradient of correspondence, with sensorimotor connections showing strong conservation and association connections showing progressive divergence. This freely available atlas provides a unified coordinate system for comparative neuroscience, enabling quantitative evaluation of where cross-species correspondence holds and where species-specific divergence emerges.

neuroscience↗

bioRxiv2025

Transmission potential of Culex and Aedes species for Madariaga virus, a member of the eastern equine encephalitis virus complex

Madariaga virus (MADV), widely distributed in Latin America, can cause severe disease in humans and equids, yet, key aspects of its transmission cycle remain unclear. To identify mosquitoes that could act as MADV vectors, we assessed the vector competence of Aedes aegypti, Ae. albopictus, Ae. taeniorhynchus, Culex tarsalis, Cx. coronator, and Cx. quinquefasciatus, following oral exposure to MADV isolated in Panama (all species) or Brazil (Ae. taeniorhynchus only). MADV RNA and infectious virus were quantified from mosquito bodies, legs, and saliva. At 14 days post-exposure, five species had virus in all biological sample types. Culex quinquefasciatus was susceptible to infection and dissemination but had no positive saliva samples. Aedes taeniorhynchus showed higher infection probabilities with MADV-BR. Time-course analysis revealed distinct dynamics in Ae. aegypti and Ae. albopictus. Our findings indicate MADV may be compatible with mosquito species present in endemic regions and areas at risk of virus introduction.

molecular biology↗

bioRxiv2025

Drosophila host defense mechanisms against filamentous fungal pathogens with diverse lifestyles

Entomopathogenic fungi serve as powerful regulators of insect populations in nature. However, how immune effectors combat fungal pathogens remains incompletely understood. We employ Drosophila melanogaster as a genetically tractable model to dissect immune defense mechanisms against diverse fungal pathogens. We show that the Toll pathway is the key determinant of immunity against all species tested regardless of their ecological strategy, primarily through resistance mechanisms that limit fungal proliferation. In addition, melanization, but not phagocytosis or the Imd pathway, also has a role in limiting fungal entry and proliferation. Additionally, we show that fungal protease detection by Persephone has a quantitatively more critical role than the glucan sensor GNBP3 in the activation of the Toll pathway upon fungal infection. Our study also reveals that the fly-obligate fungus Entomophthora muscae employs a vegetative development strategy to hide from the host immune response. These findings reveal that Drosophila immune mechanisms effectively defend against a broad range of fungal pathogens, while highlighting striking adaptations to overcome these defenses in highly specialized fungal pathogens such as E. muscae.

immunology↗